Deep Vein ThrombosisPhase 3API-CALFNCT04981327
The API-CALF Study: Apixaban to Treat Calf Vein Thrombosis
A Phase 3 study testing Apixaban 2.5 MG Oral Tablet [ELIQUIS] in people with Deep Vein Thrombosis, run by University Hospital, Geneva.
Trial summary
Isolated distal DVT (iDDVT) is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications. Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Deep Vein Thrombosis
- What is being tested?
- Apixaban 2.5 MG Oral Tablet [ELIQUIS]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,300 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2022to 31 Aug 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consecutive patients with acute (symptoms <10 days) symptomatic iDDVT diagnosed on leg CUS who have none of the following exclusion criteria and who provided informed consent to participate. Diagnosis of iDDVT is made in the presence of an incompressible distal deep vein (deep calf vein (posterior tibial, anterior tibial or peroneal veins) or muscular vein (soleal or gastrocnemius veins)).
Who cannot join
- Age < 18 years
- Ipsi or contralateral Proximal DVT
- Distal DVT involving the tibio-peroneal trunk (i.e. calf trifurcation)
- DVT occurring while on anticoagulation (started ≥48hours before DVT diagnosis); However, inpatients that developed their iDDVT while on prophylactic anticoagulation are eligible if their expected date of discharge is <6 days post randomization.
- Clinically suspected PE (patient eligible if PE ruled out with objective tests)
- Active cancer, receiving cancer treatment or cured for < 6 months
Show all 20Show fewer
- Indication for long-term therapeutic anticoagulation (e.g. atrial fibrillation, mechanical heart valve…)
- Thrombocytopenia (platelet count <100 g/l)
- Severe renal impairment (creatinine clearance <30 ml/min)
- Liver disease (including Child-Pugh Class B and C) associated with coagulopathy
- Pregnant or breast-feeding woman
- Body weight >120kg or <40 kg
- Ongoing active bleeding or condition at high risk of bleeding with anticoagulation (e.g. peptic ulcer…)
- Treatment with daily NSAIDs (aspirin ≤160 mg/day or clopidogrel ≤75 mg day permitted)
- Allergy to Apixaban
- Use of concomitant drugs that significantly interact with Apixaban: strong inhibitors of P-gp and CYP3A4 or strong inducers of CYP3A4
- Treatment with anticoagulants at therapeutic dose >2 days after DVT diagnosis
- Life expectancy < 1 year
- Enrolled in another clinical trial within previous 30 days
- Inability or refusal to provide informed consent
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Isolated distal DVT (iDDVT) is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications. Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment. However, the optimal anticoagulant intensity is uncertain, and it is plausible that the best benefit/risk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses.
The principal research question of the Apixaban to treat calf vein thrombosis (API-CALF) study is to determine whether, after a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID (experimental arm) is non inferior to Apixaban 5 mg BID (standard arm) in preventing VTE recurrence and bleeding in patients with iDDVT. Patients will be treated with Apixaban for a total of 3 months. In that perspective we will conduct an international multicentre open-label assessor-blinded study
Read the detailed description
Isolated distal deep vein thrombosis (iDDVT) is an infra-popliteal DVT, without concomitant proximal DVT and without pulmonary embolism (PE). Until recently, few large studies have focused on iDDVT, and the clinical significance and therapeutic management of iDDVT was mostly based on expert opinion and "gestalt" rather than on strong scientific data. iDDVT is the most frequent presentation of venous thromboembolic disease (VTE). Indeed, in the large French, multicentre, observational, OPTIMEV study, where all patients with suspected DVT underwent systematic whole leg compression ultrasound (CUS) exploration, iDDVT represented 56% of all DVTs. A similar high proportion of distal DVT among DVT (52.1%) was reported in Johnson's meta-analysis.
The risk of proximal extension of iDDVT to the proximal veins is substantial. In an extensive review of the literature published 15 years ago, the investigators reported that the risk of proximal extension of iDDVT, whether treated or left untreated, ranged from 0-44%, underlining the heterogeneity of the available data. Data from the CALTHRO study and CACTUS trial and extrapolation of data from management studies comparing the safety of serial proximal CUS vs. whole leg CUS for DVT diagnosis suggest that the rate of extension of untreated iDDVT to proximal deep veins was ~ 10% and up to 28% in high-risk populations, such as patients with cancer (3, 7-9). This 10% average risk of proximal extension is far above the usual 2% cut-off for an acceptable false-negative rate for negative findings in DVT diagnostic strategies. Hence, from a strict natural history standpoint, clinical significance of iDDVT is no longer in question. In summary, iDDVT is the most frequent clinical presentation of VTE and patients with iDDVT are at significant risk of proximal extension and of adverse outcomes both in the short and in the long-term.
Management of iDDVT is one of the most debated issue in the field of VTE. Thus, in all trials that validated the use of DOAC, distal location of DVT was an exclusion criterion.
While the American society of Hematology (ASH) guidelines do not comment on iDDVT specific treatment, the American college of chest physicians (ACCP) guidelines state that only 'high risk' distal DVT should be systematically treated with anticoagulation. Non high risk iDDVT could benefit from surveillance by repeated CUS. However, in the international CACTUS study, the investigators observed that a primary reason for refusal of participation and failure to fulfil recruitment was that patients and their treating physicians refused that iDDVT be left untreated. In routine clinical practice, data from observational registries showed that the majority iDDVT are treated with full dose of anticoagulants: 97% of iDDVT in the French OPTIMEV study, 98% in the Italian MASTER registry and 99% in the international RIETE registry. These therapeutic attitudes reflect physicians' beliefs (and patients' preference) that anticoagulation is important in case of iDDVT.
For proximal DVT and PE, "therapeutic" doses of anticoagulants are prescribed as use of lower doses was associated with an unacceptably high VTE risk. In contrast, for superficial vein thrombosis (SVT), "prophylactic" doses (fondaparinux 2.5mg or rivaroxaban 10 mg daily) were shown to be very effective and associated with a very low bleeding risk. Regarding iDDVT, risk of VTE recurrence and effectiveness of different dose regimen of anticoagulation are less clear and literature suggests that it could depend on patients' characteristics . Based on literature review, main risk factors for VTE extension/recurrence include cancer, calf trifurcation involvement, previous VTE, unprovoked character of DVT or presence of a permanent risk factor, and multiple vein distal vein thromboses.
In the CACTUS study, at 3 months, the proportion of extension to proximal deep veins in the therapeutic anticoagulation arm was lower than in the placebo arm (3.3% vs. 6.2% at 3 months; p=NS), but the risk of significant bleeding was significantly higher (4.1% vs. 0.0%)(3). Namely, in CACTUS, the benefit of therapeutic anticoagulation in terms of VTE risk reduction was offset by the excess in risk of bleeding.
In summary, iDDVT is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications. Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment. However, the optimal anticoagulant intensity is uncertain, and it is plausible that the best benefit/risk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses.
The principal research question of the Apixaban to treat calf vein thrombosis (API-CALF) study is to determine whether, after a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID (experimental arm) is non inferior to Apixaban 5 mg BID (standard arm) in preventing VTE recurrence and bleeding in patients with iDDVT. Patients will be treated with Apixaban for a total of 3 months. In that perspective we will conduct an international multicentre open-label assessor-blinded study
- Conditions
- Deep Vein Thrombosis
- Being tested
- Apixaban 2.5 MG Oral Tablet [ELIQUIS]
- Keywords
- Isolated distal deep vein thrombosis, Anticoagulation, Direct oral anticoagulants
- Medical subject headings
- Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apixaban 2.5 MG Oral Tablet [ELIQUIS]Drug
Also called Apixaban 5 MG Oral Tablet
Apixaban 5 MG BID versus Apixaban 2.5 MG BID
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | After a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID during 3 months. Receives: Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS] |
| Standard | Active comparator | After a conventional course of 7 days of Apixaban 10 mg BID, Apixaban 5 mg BID during 3 months. Receives: Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of i) symptomatic VTE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death.
The primary outcome is a composite of rate of i) symptomatic VTE (includes iDDVT involving a new distal deep vein, proximal DVT or PE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death.
Measured: 1 year
Secondary outcomes (5)
Individual components of the composite endpoint at 3 months and 1 year - Generic and venous disease-specific QOL scores at 1 year - Patient's compliance with treatment at 3 months - Serious adverse events during follow-up - PTS as measured at 1 year
as above
Measured: 1 year
Generic and venous disease-specific QOL scores at 1 year
QOL score
Measured: 1 year
Patient's observance with treatment at 3 months
Observance of the patient
Measured: 3 months
Serious adverse events during follow-up
Adverse events
Measured: 1 year
PTS as measured at 1 year
Post thrombotic syndrome assessed with the Villalta scale
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2021
- Study start1 Sep 2022 (estimated)
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Deep Vein ThrombosisStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre
- Responsible party
- Principal investigator, Marc Righini, University Hospital, Geneva
- Investigators
- Jean-Philippe Galanaud, MD, PhD, Principal investigator, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, CanadaMarc Righini, MD, Principal investigator, Geneva University Hospital, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04981327
- Sponsor's protocol ID
- APICALF
- Acronym
- API-CALF
- Status last verified
- Jul 2021
- First submitted
- 7 Jul 2021
- Last updated
- 29 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual research subjects' data cannot legally nor ethically be made available to non authorised people (HRA, cf. §7). According to the research subjects' informed consent, only the sponsor, the investigation team, reviewers, auditors and inspection authorities are entitled to access such data.
Publications
Galanaud JP, Bosson JL, Quere I. Risk factors and early outcomes of patients with symptomatic distal vs. proximal deep-vein thrombosis. Curr Opin Pulm Med. 2011 Sep;17(5):387-91. doi: 10.1097/MCP.0b013e328349a9e3.
PubMed 21832920Schellong SM. Distal DVT: worth diagnosing? Yes. J Thromb Haemost. 2007 Jul;5 Suppl 1:51-4. doi: 10.1111/j.1538-7836.2007.02490.x.
PubMed 17635708Righini M, Galanaud JP, Guenneguez H, Brisot D, Diard A, Faisse P, Barrellier MT, Hamel-Desnos C, Jurus C, Pichot O, Martin M, Mazzolai L, Choquenet C, Accassat S, Robert-Ebadi H, Carrier M, Le Gal G, Mermilllod B, Laroche JP, Bounameaux H, Perrier A, Kahn SR, Quere I. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol. 2016 Dec;3(12):e556-e562. doi: 10.1016/S2352-3026(16)30131-4. Epub 2016 Nov 8.
PubMed 27836513Galanaud JP, Sevestre-Pietri MA, Bosson JL, Laroche JP, Righini M, Brisot D, Boge G, van Kien AK, Gattolliat O, Bettarel-Binon C, Gris JC, Genty C, Quere I; OPTIMEV-SFMV Investigators. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009 Sep;102(3):493-500. doi: 10.1160/TH09-01-0053.
PubMed 19718469Johnson SA, Stevens SM, Woller SC, Lake E, Donadini M, Cheng J, Labarere J, Douketis JD. Risk of deep vein thrombosis following a single negative whole-leg compression ultrasound: a systematic review and meta-analysis. JAMA. 2010 Feb 3;303(5):438-45. doi: 10.1001/jama.2010.43.
PubMed 20124539Righini M, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Curr Opin Pulm Med. 2008 Sep;14(5):408-13. doi: 10.1097/MCP.0b013e32830460ea.
PubMed 18664970Palareti G, Cosmi B, Lessiani G, Rodorigo G, Guazzaloca G, Brusi C, Valdre L, Conti E, Sartori M, Legnani C. Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010 Nov;104(5):1063-70. doi: 10.1160/TH10-06-0351. Epub 2010 Aug 5.
PubMed 20694281Bernardi E, Camporese G, Buller HR, Siragusa S, Imberti D, Berchio A, Ghirarduzzi A, Verlato F, Anastasio R, Prati C, Piccioli A, Pesavento R, Bova C, Maltempi P, Zanatta N, Cogo A, Cappelli R, Bucherini E, Cuppini S, Noventa F, Prandoni P; Erasmus Study Group. Serial 2-point ultrasonography plus D-dimer vs whole-leg color-coded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA. 2008 Oct 8;300(14):1653-9. doi: 10.1001/jama.300.14.1653.
PubMed 18840838Gibson NS, Schellong SM, Kheir DY, Beyer-Westendorf J, Gallus AS, McRae S, Schutgens RE, Piovella F, Gerdes VE, Buller HR. Safety and sensitivity of two ultrasound strategies in patients with clinically suspected deep venous thrombosis: a prospective management study. J Thromb Haemost. 2009 Dec;7(12):2035-41. doi: 10.1111/j.1538-7836.2009.03635.x. Epub 2009 Oct 8.
PubMed 19817986Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-e418S. doi: 10.1378/chest.11-2299.
PubMed 22315267Galanaud JP, Sevestre MA, Genty C, Pernod G, Quere I, Bosson JL. Is it useful to also image the asymptomatic leg in patients with suspected deep vein thrombosis?: comment. J Thromb Haemost. 2015 Nov;13(11):2127-30. doi: 10.1111/jth.13123. Epub 2015 Sep 30. No abstract available.
PubMed 26332772Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2014 Mar 20;123(12):1802-9. doi: 10.1182/blood-2013-10-512616. Epub 2014 Jan 28.
PubMed 24472834Palareti G, Schellong S. Isolated distal deep vein thrombosis: what we know and what we are doing. J Thromb Haemost. 2012 Jan;10(1):11-9. doi: 10.1111/j.1538-7836.2011.04564.x.
PubMed 22082302Righini M. Is it worth diagnosing and treating distal deep vein thrombosis? No. J Thromb Haemost. 2007 Jul;5 Suppl 1:55-9. doi: 10.1111/j.1538-7836.2007.02468.x.
PubMed 17635709Masuda EM, Kistner RL, Musikasinthorn C, Liquido F, Geling O, He Q. The controversy of managing calf vein thrombosis. J Vasc Surg. 2012 Feb;55(2):550-61. doi: 10.1016/j.jvs.2011.05.092. Epub 2011 Oct 26.
PubMed 22032881
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The API-CALF Study: Apixaban to Treat Calf Vein Thrombosis
- ClinicalTrials.gov ID
- NCT04981327
- Acronym / sponsor ID
- API-CALF / APICALF
- Conditions
- Deep Vein Thrombosis
- Keywords
- Isolated distal deep vein thrombosis, Anticoagulation, Direct oral anticoagulants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,300 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre
- Study start
- 1 Sep 2022 (estimated)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 29 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Isolated distal DVT (iDDVT) is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications. Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment. However, the optimal anticoagulant intensity is uncertain, and it is plausible that the best benefit/risk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses.
The principal research question of the Apixaban to treat calf vein thrombosis (API-CALF) study is to determine whether, after a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID (experimental arm) is non inferior to Apixaban 5 mg BID (standard arm) in preventing VTE recurrence and bleeding in patients with iDDVT. Patients will be treated with Apixaban for a total of 3 months. In that perspective we will conduct an international multicentre open-label assessor-blinded study
Detailed description
Isolated distal deep vein thrombosis (iDDVT) is an infra-popliteal DVT, without concomitant proximal DVT and without pulmonary embolism (PE). Until recently, few large studies have focused on iDDVT, and the clinical significance and therapeutic management of iDDVT was mostly based on expert opinion and "gestalt" rather than on strong scientific data. iDDVT is the most frequent presentation of venous thromboembolic disease (VTE). Indeed, in the large French, multicentre, observational, OPTIMEV study, where all patients with suspected DVT underwent systematic whole leg compression ultrasound (CUS) exploration, iDDVT represented 56% of all DVTs. A similar high proportion of distal DVT among DVT (52.1%) was reported in Johnson's meta-analysis.
The risk of proximal extension of iDDVT to the proximal veins is substantial. In an extensive review of the literature published 15 years ago, the investigators reported that the risk of proximal extension of iDDVT, whether treated or left untreated, ranged from 0-44%, underlining the heterogeneity of the available data. Data from the CALTHRO study and CACTUS trial and extrapolation of data from management studies comparing the safety of serial proximal CUS vs. whole leg CUS for DVT diagnosis suggest that the rate of extension of untreated iDDVT to proximal deep veins was ~ 10% and up to 28% in high-risk populations, such as patients with cancer (3, 7-9). This 10% average risk of proximal extension is far above the usual 2% cut-off for an acceptable false-negative rate for negative findings in DVT diagnostic strategies. Hence, from a strict natural history standpoint, clinical significance of iDDVT is no longer in question. In summary, iDDVT is the most frequent clinical presentation of VTE and patients with iDDVT are at significant risk of proximal extension and of adverse outcomes both in the short and in the long-term.
Management of iDDVT is one of the most debated issue in the field of VTE. Thus, in all trials that validated the use of DOAC, distal location of DVT was an exclusion criterion.
While the American society of Hematology (ASH) guidelines do not comment on iDDVT specific treatment, the American college of chest physicians (ACCP) guidelines state that only 'high risk' distal DVT should be systematically treated with anticoagulation. Non high risk iDDVT could benefit from surveillance by repeated CUS. However, in the international CACTUS study, the investigators observed that a primary reason for refusal of participation and failure to fulfil recruitment was that patients and their treating physicians refused that iDDVT be left untreated. In routine clinical practice, data from observational registries showed that the majority iDDVT are treated with full dose of anticoagulants: 97% of iDDVT in the French OPTIMEV study, 98% in the Italian MASTER registry and 99% in the international RIETE registry. These therapeutic attitudes reflect physicians' beliefs (and patients' preference) that anticoagulation is important in case of iDDVT.
For proximal DVT and PE, "therapeutic" doses of anticoagulants are prescribed as use of lower doses was associated with an unacceptably high VTE risk. In contrast, for superficial vein thrombosis (SVT), "prophylactic" doses (fondaparinux 2.5mg or rivaroxaban 10 mg daily) were shown to be very effective and associated with a very low bleeding risk. Regarding iDDVT, risk of VTE recurrence and effectiveness of different dose regimen of anticoagulation are less clear and literature suggests that it could depend on patients' characteristics . Based on literature review, main risk factors for VTE extension/recurrence include cancer, calf trifurcation involvement, previous VTE, unprovoked character of DVT or presence of a permanent risk factor, and multiple vein distal vein thromboses.
In the CACTUS study, at 3 months, the proportion of extension to proximal deep veins in the therapeutic anticoagulation arm was lower than in the placebo arm (3.3% vs. 6.2% at 3 months; p=NS), but the risk of significant bleeding was significantly higher (4.1% vs. 0.0%)(3). Namely, in CACTUS, the benefit of therapeutic anticoagulation in terms of VTE risk reduction was offset by the excess in risk of bleeding.
In summary, iDDVT is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications. Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment. However, the optimal anticoagulant intensity is uncertain, and it is plausible that the best benefit/risk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses.
The principal research question of the Apixaban to treat calf vein thrombosis (API-CALF) study is to determine whether, after a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID (experimental arm) is non inferior to Apixaban 5 mg BID (standard arm) in preventing VTE recurrence and bleeding in patients with iDDVT. Patients will be treated with Apixaban for a total of 3 months. In that perspective we will conduct an international multicentre open-label assessor-blinded study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS]After a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID during 3 months. |
| Standard | Active comparator | Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS]After a conventional course of 7 days of Apixaban 10 mg BID, Apixaban 5 mg BID during 3 months. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Consecutive patients with acute (symptoms <10 days) symptomatic iDDVT diagnosed on leg CUS who have none of the following exclusion criteria and who provided informed consent to participate. Diagnosis of iDDVT is made in the presence of an incompressible distal deep vein (deep calf vein (posterior tibial, anterior tibial or peroneal veins) or muscular vein (soleal or gastrocnemius veins)).
Key exclusion criteria (20 listed)
- Age < 18 years
- Ipsi or contralateral Proximal DVT
- Distal DVT involving the tibio-peroneal trunk (i.e. calf trifurcation)
- DVT occurring while on anticoagulation (started ≥48hours before DVT diagnosis); However, inpatients that developed their iDDVT while on prophylactic anticoagulation are eligible if their expected date of discharge is <6 days post randomization.
- Clinically suspected PE (patient eligible if PE ruled out with objective tests)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Apixaban 2.5 MG Oral Tablet [ELIQUIS]Also: Apixaban 5 MG Oral TabletApixaban 5 MG BID versus Apixaban 2.5 MG BID | Drug | Experimental, Standard |
Primary outcome
Rate of i) symptomatic VTE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death.
Time frame: 1 year
The primary outcome is a composite of rate of i) symptomatic VTE (includes iDDVT involving a new distal deep vein, proximal DVT or PE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death.
5 secondary outcomes
Individual components of the composite endpoint at 3 months and 1 year - Generic and venous disease-specific QOL scores at 1 year - Patient's compliance with treatment at 3 months - Serious adverse events during follow-up - PTS as measured at 1 year
Time frame: 1 year
Generic and venous disease-specific QOL scores at 1 year
Time frame: 1 year
Patient's observance with treatment at 3 months
Time frame: 3 months
Serious adverse events during follow-up
Time frame: 1 year
PTS as measured at 1 year
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2021.
- Results publication: PubMed 21832920Galanaud JP, Bosson JL, Quere I. Risk factors and early outcomes of patients with symptomatic distal vs. proximal deep-vein thrombosis. Curr Opin Pulm Med. 2011 Sep;17(5):387-91. doi: 10.1097/MCP.0b013e328349a9e3.
- Results publication: PubMed 17635708Schellong SM. Distal DVT: worth diagnosing? Yes. J Thromb Haemost. 2007 Jul;5 Suppl 1:51-4. doi: 10.1111/j.1538-7836.2007.02490.x.
- Results publication: PubMed 27836513Righini M, Galanaud JP, Guenneguez H, Brisot D, Diard A, Faisse P, Barrellier MT, Hamel-Desnos C, Jurus C, Pichot O, Martin M, Mazzolai L, Choquenet C, Accassat S, Robert-Ebadi H, Carrier M, Le Gal G, Mermilllod B, Laroche JP, Bounameaux H, Perrier A, Kahn SR, Quere I. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol. 2016 Dec;3(12):e556-e562. doi: 10.1016/S2352-3026(16)30131-4. Epub 2016 Nov 8.
- Results publication: PubMed 19718469Galanaud JP, Sevestre-Pietri MA, Bosson JL, Laroche JP, Righini M, Brisot D, Boge G, van Kien AK, Gattolliat O, Bettarel-Binon C, Gris JC, Genty C, Quere I; OPTIMEV-SFMV Investigators. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009 Sep;102(3):493-500. doi: 10.1160/TH09-01-0053.
- Results publication: PubMed 20124539Johnson SA, Stevens SM, Woller SC, Lake E, Donadini M, Cheng J, Labarere J, Douketis JD. Risk of deep vein thrombosis following a single negative whole-leg compression ultrasound: a systematic review and meta-analysis. JAMA. 2010 Feb 3;303(5):438-45. doi: 10.1001/jama.2010.43.
- Results publication: PubMed 18664970Righini M, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Curr Opin Pulm Med. 2008 Sep;14(5):408-13. doi: 10.1097/MCP.0b013e32830460ea.
- Results publication: PubMed 20694281Palareti G, Cosmi B, Lessiani G, Rodorigo G, Guazzaloca G, Brusi C, Valdre L, Conti E, Sartori M, Legnani C. Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010 Nov;104(5):1063-70. doi: 10.1160/TH10-06-0351. Epub 2010 Aug 5.
- Results publication: PubMed 18840838Bernardi E, Camporese G, Buller HR, Siragusa S, Imberti D, Berchio A, Ghirarduzzi A, Verlato F, Anastasio R, Prati C, Piccioli A, Pesavento R, Bova C, Maltempi P, Zanatta N, Cogo A, Cappelli R, Bucherini E, Cuppini S, Noventa F, Prandoni P; Erasmus Study Group. Serial 2-point ultrasonography plus D-dimer vs whole-leg color-coded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA. 2008 Oct 8;300(14):1653-9. doi: 10.1001/jama.300.14.1653.
- Results publication: PubMed 19817986Gibson NS, Schellong SM, Kheir DY, Beyer-Westendorf J, Gallus AS, McRae S, Schutgens RE, Piovella F, Gerdes VE, Buller HR. Safety and sensitivity of two ultrasound strategies in patients with clinically suspected deep venous thrombosis: a prospective management study. J Thromb Haemost. 2009 Dec;7(12):2035-41. doi: 10.1111/j.1538-7836.2009.03635.x. Epub 2009 Oct 8.
- Results publication: PubMed 22315267Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-e418S. doi: 10.1378/chest.11-2299.
- Results publication: PubMed 26332772Galanaud JP, Sevestre MA, Genty C, Pernod G, Quere I, Bosson JL. Is it useful to also image the asymptomatic leg in patients with suspected deep vein thrombosis?: comment. J Thromb Haemost. 2015 Nov;13(11):2127-30. doi: 10.1111/jth.13123. Epub 2015 Sep 30. No abstract available.
- Results publication: PubMed 24472834Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2014 Mar 20;123(12):1802-9. doi: 10.1182/blood-2013-10-512616. Epub 2014 Jan 28.
- Individual participant dataSharing planned: No. Individual research subjects' data cannot legally nor ethically be made available to non authorised people (HRA, cf. §7). According to the research subjects' informed consent, only the sponsor, the investigation team, reviewers, auditors and inspection authorities are entitled to access such data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jean-Philippe Galanaud, MD, PhD principal investigator
Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Canada
Marc Righini, MD principal investigator
Geneva University Hospital, Switzerland
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban 2.5 MG Oral Tablet [ELIQUIS] in people with Deep Vein Thrombosis, run by University Hospital, Geneva.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-Philippe Galanaud, MD, PhD (001, Jean-Philippe.Galanaud@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of i) symptomatic VTE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04981327, which also lists 31 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2021.